The present invention relates to optical devices and methods for screening of cervical tissue abnormalities.
Early detection of a variety of pathologies has been shown to dramatically improve the therapeutic outcome for such pathologies. This is particularly true with cancer, and specifically with cancer of the cervix. In the case of cancer of the cervix and other cervix anomalies, the pap smear test has been used for many years as a screening method for the detection of pre-cancerous conditions as well as for the detection of cancer. Unfortunately, this method suffers from excessive errors and results in too many false positive as well as false negative determinations, which increases the overall cost to the health care system. The method requires the physician to scrape cells from the surface of the cervix and transfer the cells to a laboratory where a cytopathologist examines them under a microscope. Statistics on the false positive readings of pap smears range as high as 30% and false negative error rate of 20% to 30% associated with insufficient cell readings or inexpert readings of pap smears are normal as well.
In the case of false negative determinations, additional colposcopic examinations and biopsies of the cervix are carried out on patients with normal tissue, overloading the health care system unnecessarily. On the other hand, false negative pap smears allow the pathologies to evolve to full cancers that could have been treated earlier at much lower costs and with better outcomes.
Fluorescence spectroscopy, which is capable of distinguishing histologically normal and histologically abnormal tissue, has been used for the detection of cervical neoplasia by comparing fluorescence of a suspicious area of the cervix with normal tissue. Since the location of abnormal tissue is often difficult to determine by eye, this approach tends to require highly trained practitioners to determine normal tissue.
In other tissues types, pre-cancerous conditions present themselves in ways that make identification of potential abnormal sites over normal sites much easier than in the cervix. In the colon, for example, the presentation of polyps forming on the interior wall is an indication of possible malignant growth. Spectroscopic studies comparing tissue responses of polyp regions from non-polyp regions show a high degree of difference in the optical signatures of the tissue. This is to be expected, considering the morphologic differences in the tissues. In the cervix, however, surface changes caused by the presence of lesions are often difficult, if not impossible, to see. This indicates that the tissue differences between normal and abnormal tissue are often very subtle, and optical techniques must attempt to distinguish these subtle features.
The tissue fluorescence may be excited, for example, by excitation with UV light. Other spectroscopic methods employ multiple fluorescence excitation wavelengths and use discrimination functions, which frequently cannot easily classify the health of the tissue, even when comparing spectra from the same cervix. Accordingly, these spectroscopic methods have little predictive power when used with other cervixes since each xe2x80x9cstandardxe2x80x9d (normal tissue) invariably may have to be determined for each cervix screened.
It would therefore be desirable to provide a screening system and method that provide an immediate indication of the health of the cervical tissue and could replace a pap smear test as a screening modality, is simpler to perform, does not depend on the specific cervix screened, and can be administered by personnel having minimal medical training.
The invention is directed to provide a system and a method of optically classifying cervical tissue into pathological classes, without a priori knowledge if a tissue and/or which tissue may or may not be normal. The classification is based on a statistical algorithm which associates the tissue with the respective tissue classes by computing a xe2x80x9cdistancexe2x80x9d between a tissue response and a training (reference) response. The tissue is assigned to the pathological class which produces the smallest distance.
According to one aspect of the invention, a source of optical radiation is provided which induces at least one of a fluorescence and backscatter response in the cervical tissue. A detector detects the response induced in the cervical tissue and produces a response signal. A processor compares the response signal with reference signals obtained from cervical tissue samples of known pathology by computing a distance between the response signal and the reference signals. The reference signals are grouped into at least two pathological classes and the cervical tissue producing the response signal is assigned to the class which produces the smallest distance.
According to another aspect of the invention, a diagnostic system produces a map of the cervix according to pathological classes. A source of optical radiation induces at least one of a fluorescence and backscatter response in cervical tissue, wherein the source is scanned in a predetermined pattern over tissue sites of at least a portion of the cervix. A detector detects the response induced in the cervical tissue and produces a response signal. A processor compares the response signal with reference signals obtained from cervical tissue samples of known pathology by computing a distance between the response signal and the reference signals from the different tissue sites. The reference signals are grouped into at least two pathological classes and the cervical tissue which produces the response signal at the different tissue sites is assigned to the class which produces the smallest distance for that site. The assigned classes for the different tissue sites can be rendered to produce the map of the cervix.
According to yet another aspect of the invention, a method is provided of optically classifying cervical tissue into pathological classes, which includes exciting the cervical tissue with optical radiation and inducing at least one of a fluorescence and backscatter response in the cervical tissue, detecting the response induced in the cervical tissue and producing a response signal, comparing the response signal with reference signals which are obtained from cervical tissue samples of known pathology and grouped into at least two pathological classes, computing a distance between the response signal and the reference signals, and assigning the cervical tissue to the class which produces the response signal having the smallest distance.
According to still another aspect of the invention, a method is provided of optically classifying cervical tissue into pathological classes, which includes exciting the cervical tissue with optical radiation and detecting a fluorescence response in the cervical tissue, comparing the fluorescence response with a fluorescence reference response which were obtained from cervical tissue samples of known pathology and grouped into at least two pathological classes, by computing a first distance between the fluorescence response and the reference response and assigning the cervical tissue to the class which produces the response signal having the smallest first distance. The method further includes detecting a backscatter response from the cervical tissue at the same location in the cervix, comparing the backscatter response with a backscatter reference response which were obtained from cervical tissue samples of known pathology and grouped into the at least two pathological classes, by computing a second distance between the backscatter response and the backscatter reference response and assigning the cervical tissue to the class which produces the backscatter response signal having the smallest second distance. If the class of the cervical tissue based on the first distance is identical to the class of the cervical tissue based on the second distance, then the cervical tissue is classified into the class representing both the first and second distance. On the other hand, if the class of the cervical tissue based on the first distance is different from the class of the cervical tissue based on the second distance, then the fluorescence response is combined with the backscatter response and a third distance between the combined response and a respective combined fluorescence and backscatter reference response is computed. The cervical tissue is assigned to the class which produces the combined response signal having the smallest third distance.
Embodiments of the invention may include one or more of the following features. The computed distance may be a Mahalanobis distance, which may be computed by including Quadratic Discriminant Analysis (QDA) and/or Regularized Discriminant Analysis (RDA) to eliminate problems caused by singularities. The source of the optical radiation, which may be the cervical probe, and/or the detector may be placed so as not to contact the cervical tissue. The at least two pathological classes may include CIN (cervical intraepithelial neoplasia) and NED (squamus normal or no evidence of disease) tissue. The source of optical radiation may be an ultraviolet (UV) source, such as a UV laser, for example, a frequency-tripled Nd:YAG laser, a nitrogen laser or a He-Cd laser, emitting at a wavelength between 300 and 400 nm. Alternatively or in addition, the source of optical radiation is a broadband light source emitting in the visible/infrared spectral range, such as a xenon lamp. the detector may includes at least two detection systems, with a first system detecting the fluorescence response and a second system detecting the backscatter response. The response signal may be a normalized signal obtained, for example, by scaling the fluorescence response and/or the backscatter response with respect to the other of the backscatter response and/or fluorescence response. The backscatter response may be calibrated against a target having a known spectral reflectivity, for example, a reflectivity of approximately 10%. The reference signals may be stored in a memory.
Further features and advantages of the present invention will be apparent from the following description of certain preferred embodiments and from the claims.